The Major Cold Inducible Gene of S. aureus, cspB, modulates susceptibility to antimicrobials Público
Duval, Brea Dianamarie (2010)
Published
Abstract
The Major Cold Inducible Gene of S. aureus,
cspB,
Modulates Susceptibility to Antimicrobials
By Brea Duval
Staphylococcus aureus is a major human pathogen causing a
varied group of
diseases ranging in severity from mild skin to invasive, often
deadly infections that can
impact the function of multiple organs and systems. While part of
the normal human
flora, problems with antibiotic resistant strains have been ever
increasing and the arsenal
of effective drugs available for treatment has been steadily
dwindling. S. aureus is able to
cause such diverse diseases because of its ability to survive a
variety of environments,
which would subject the bacteria to changes in temperature, pH,
ionic strength and
mediators of innate immunity. Previous work from our laboratory
defined the role of the
major cold shock protein of S. aureus, CspA, in the
bacteria's response to cold stress as
well as its role in resistance to antimicrobial peptides. Two other
members of the cspA
family cold shock protein-encoding genes, cspB and
cspC, were found in the genome of
strain COL, a methicillin resistant clinical isolate.
Previous microarray analysis identified cspB as the major
cold-inducible gene in
S. aureus. Therefore, the aim of this work was to define the
role of cspB found in strain
COL in antibiotic resistance and cold stress. In addition to having
an important role under
cold-shock conditions, CspB seems to have important functions under
normal (37 °C)
growth conditions. We found that insertional inactivation of
cspB resulted in dramatic
phenotypic changes that resembled those previously ascribed to
staphylococcal small
colony variants (SCVs). These changes include loss of pigment, slow
growth, and an
increase in resistance to several clinically relevant
antimicrobials. Interestingly, while
complementation of a cspB insertional mutant showed
restoration of all of these
phenotypic changes to wild type levels, the two notable exceptions
were lack of complete
complementation of biofilm forming capacity and loss of resistance
to methicillin. This
loss of methicillin resistance was shown to be due to loss of the
type I SCC mec cassette.
Taken together, this data suggests that cspB plays important
role in many aspects of
staphylococcal pathogenesis including suggesting a novel role for
this stress response
protein in involvement in the SCV phenotype.
Table of Contents
Table of Contents
Abstract
Dedication
Acknowledgements
List of Tables and Figures
Chapter 1:
Introduction………………………………………………………………1
Chapter 2: Altered Growth, Pigmentation and Antimicrobial
Susceptibility Properties
of Staphylococcus aureus Due to Loss of the Major Cold Shock
Gene cspB……….100
Chapter 3: Unpublished
Observations……………………………………………….137
Chapter 4: Final
Discussion…...……………………………………………………..155
List of Figures and Tables
Chapter 1
Figure 1: Evasion of Host Innate Defenses by S. aureus
Figure 2: Diagram of the Five Major Scc mec Types
Chapter 2
Table 1: Bacterial Strains and Plasmids
Table 2: Oligonucleotides used
Table 3: MIC Data Summary
Table 4: Influence of growth and assay temperature on the
antibiotic
of S. aureus
Figure 1: Comparative Densitometry of Selected Transcripts
Figure 2: Pigment Production by Staphylococcal Strains
Figure 3: Growth Differences Between Staphylococcal Strains
Figure 4: Disk Diffusion Analysis of Selected Antimicrobials
Figure 5: Loss of the Type I SCC mec cassette in Strains BD1
and BD2
Chapter 3
Figure 1: SEM Analysis of Staphylococcal Strains
Figure 2: Microarray Analysis of Strain BD1 vs. Strain COL
Figure 3: Proposed model for CspB dependent regulation of the
ica locus by TcaR
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